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Modulation of VGCCs by G-Protein Coupled Receptors and Their Second Messengers

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Voltage-Gated Calcium Channels

Abstract

Voltage-gated calcium channels (VGCCs) are essential for transforming electrical signals such as action potentials into biochemical and eventually physiological responses through the control of intracellular calcium. They mediate the depolarization of cells and increase the intracellular Ca2+ levels to regulate a variety of physiological events including neurotransmission, secretion, enzyme activity, cellular differentiation, gene expression, smooth muscle contraction, and pacemaker activity. Deficits in VGCCs function can lead to epilepsy, migraine, ataxia, autism, cardiac arrythmias, and pain. Therefore, careful modulation of VGCCs is vital. In this chapter, we will discuss the modulation of VGCCs by different G protein-coupled receptors and their downstream effectors such as G proteins, lipids, kinases, and synaptic associated proteins focusing primarily on the central nervous system and heart. Moreover, we will describe the underlying mechanisms that G proteins and their downstream second messengers use to control VGCCs.

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Abbreviations

5-HT:

Serotonin

AA:

Arachidonic acid

AC:

Adenylyl cyclase

AGS:

Activator of G protein signaling

AID:

α interaction domain

AKAP:

A-kinase anchoring protein

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AR:

adrenoceptor

BDNF:

Brain-derived neurotrophic factor

Ca2+:

Calcium

CaBP:

Ca2+ binding protein

CaM:

Calmodulin

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

cAMP:

Cyclic adenosine monophosphate

CaS:

Ca2+ sensor

CB:

Cannabinoid receptor

cGMP:

Cyclic guanosine monophosphate

CNS:

Central nervous system

CRF:

Corticotropin-releasing factor

CTX:

Cholera toxin

D1R:

Dopamine D1 receptor 2

D2R:

Dopamine D2 receptor

DAG:

Diacylglycerol

DRG:

Dorsal root ganglion

ER:

Endoplasmatic reticulum

FGF:

Fibroblast growth factor

FGFR1:

Fibroblast growth factor type 1 receptor

FRET:

Fluorescence resonance energy transfer

GABA:

Gamma-aminobutyric acid

GDP:

Guanosine diphosphate

Ghrelin:

Growth hormone release inducing

GHS-R1a:

Growth hormone secretagogue receptor 1a

GID:

G protein interaction domain

GPCRs:

G protein-coupled receptors

GRK:

G protein coupled receptor kinase

GTP:

Guanosine triphosphate

HEK:

Human embryonic kidney

ICa:

Ca2+ current

IGF-1:

Insulin-like growth factor 1

IP3:

Inositol triphosphate

Kir:

Inward rectifying potassium channel

LPA:

Lysophosphatidic acid

LTD:

Long term depression

LTP:

Long-term potentiation

M1R:

Muscarinic receptor 1

MAPK:

Mitogen-activated protein kinase

mGluR:

Metabotropic glutamate receptor

NA:

noradrenaline

Na:

sodium

NCS-1:

Neural Ca2+ sensor-1

NO:

Nitric oxide

OAG:

1,2-Oleoylacetyl-glycerol

PDE:

Phosphodiesterase

PI3K:

Phosphatidylinositol 3-kinase

PIP2:

Phosphatidylinositol 4,5-bisphosphate

PKA:

Protein kinase A

PKC:

Protein kinase C

PKG:

Protein kinase G

PKI:

Protein kinase A inhibitor

PLC:

Phospholipase C

PMA:

Phorbol-myristate 13-acetate

PP:

protein phosphatase

PSD-95:

Postsynaptic density protein-95

PTK:

Protein tyrosine kinase

PTX:

Pertussis toxin

RGS:

Regulators of G protein signaling

ROCK:

Rho-associated protein kinase

SNAP-25:

Synaptosomal-associated protein

SNAREs:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors

SST:

Somatostatin receptor

Thr:

Threonine

VGCCs:

Voltage-gated calcium channels

VILIP-2:

Visinin-like protein-2

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Authors and Affiliations

  1. Behavioral Neuroscience, Ruhr-University Bochum, Bochum, Germany

    Melanie D. Mark & Jan Claudius Schwitalla

  2. Department of Zoology and Neurobiology, Ruhr-University Bochum, Bochum, Germany

    Stefan Herlitze

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  1. Melanie D. Mark
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  2. Jan Claudius Schwitalla
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  1. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

    Gerald Werner Zamponi

  2. Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

    Norbert Weiss

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Mark, M.D., Schwitalla, J.C., Herlitze, S. (2022). Modulation of VGCCs by G-Protein Coupled Receptors and Their Second Messengers. In: Zamponi, G.W., Weiss, N. (eds) Voltage-Gated Calcium Channels . Springer, Cham. https://doi.org/10.1007/978-3-031-08881-0_7

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